B. J. Messmer

Myocyte degeneration and cell death in hibernating human myocardium

OBJECTIVESnThe aim of this study was to analyze the morphologic characteristics of myocyte degeneration leading to replacement fibrosis in hibernating myocardium by use of electron microscopy and immunohistochemical techniques.nnnBACKGROUNDnData on the ultrastructure and the cytoskeleton of cardiomyocytes in myocardial hibernation are scarce. Incomplete or delayed functional recovery might be due to variable degree of cardiomyocyte degeneration in hibernating myocardium.nnnMETHODSnIn 24 patients, regional wall motion abnormalities were analyzed by use of the centerline method before and 6 +/- 1 months after coronary artery bypass surgery. Preoperative technetium-99m sestamibi uptake was measured by single-photon emission computed tomography for assessing regional perfusion. Fluorine-18 fluorodeoxyglucose uptake was measured by positron emission tomography to assess glucose metabolism. Transmural biopsy specimens were taken during coronary artery bypass surgery from the center of the hypocontractile area of the anterior wall.nnnRESULTSnThe myocytes showed varying signs of mild-to-severe degenerative changes and an increased degree of fibrosis. Immunohistochemical analysis demonstrated disruption of the cytoskeletal proteins titin and alpha-actinin. Electron microscopy of the cell organelles and immunohistochemical analysis of the cytoskeleton showed a similarity in the degree of degenerative alterations. Group 1 (n = 11) represented patients with only minor structural alterations, whereas group 2 (n = 13) showed severe morphologic degenerative changes. Wall motion abnormalities showed postoperative improvements, and nuclear imaging revealed a perfusion-metabolism mismatch without significant differences between the groups.nnnCONCLUSIONSnLong-term hypoperfusion causes different degrees of morphologic alterations leading to degeneration. Preoperative analysis of regional contractility and perfusion-metabolism imaging does not distinguish the severity of morphologic alterations nor the functional outcome after revascularization. The insufficient act of self-preservation in hibernating myocardium may lead to a progressive structural degeneration with an incomplete and delayed recovery of function after restoration of blood flow.

Prolonged Myocardial Hibernation Exacerbates Cardiomyocyte Degeneration and Impairs Recovery of Function After Revascularization

OBJECTIVESnWe sought to define the effects of time on contractile function, morphology and functional recovery after coronary revascularization in patients with dysfunctional but viable (hibernating) myocardium.nnnBACKGROUNDnFunctional recovery after coronary artery bypass graft surgery in patients with chronic myocardial hibernation is incomplete or delayed. The proposed cause is a progressive temporal degeneration of cardiomyocytes.nnnMETHODSnIn 32 patients with multivessel coronary disease, regional wall motion analysis was performed in hypoperfused but metabolically active areas before and 6 months after bypass surgery. During bypass surgery, transmural biopsy samples were obtained from the center of the hypokinetic zone for light and electron microscopic analyses. The proposed duration of myocardial hibernation was retrospectively assessed.nnnRESULTSnPatients with a subacute hibernating condition (<50 days) demonstrated a higher preoperative ejection fraction (EF, 50+/-8%), and a better preserved wall motion (WM) in the supraapical wall (-1.4+/-0.4) than did patients with intermediate-term (>50 days, EF 37+/-9%, p < 0.05; WM -2.4+/-1.5, p = 0.08) or chronic (>6 months, EF 40+/-14%, WM -2.7+/-0.9, p < 0.005) ischemia. Structural degeneration correlated with the duration of ischemia (r = 0.56, p < 0.05). Postoperative recovery of function was enhanced in patients with a short history of hibernation compared with patients with an intermediate-term or chronic condition (EF 60+/-10% vs. 40+/-10%, p < 0.001, and vs. 47+/-14%, p < 0.05).nnnCONCLUSIONSnHibernating myocardium exhibits time-dependent deterioration due to progressive structural degeneration with enhanced fibrosis. Early revascularization should be attempted to salvage the jeopardized tissue and improve postoperative outcome.

Percutaneous transluminal coronary angioplasty in patients with stable and unstable angina pectoris: Analysis of early and late results

Percutaneous transluminal coronary angioplasty (PTCA) was performed in 50 patients with stable and in 50 patients with unstable angina pectoris, each patient showing an isolated stenosis of more than 80% of the cross-sectional area of a single coronary artery. The technical success rate was 66% in the stable groups (26 of 37 patients [70%] with left anterior descending artery [LAD], 7 of 12 patients [58%] with right coronary artery [RCA]) and 74% in the unstable group (27 of 34 patients [79%] with LAD, 10 of 15 patients [67%] with (RCA). The increase in stenotic area in the unstable group exceeding that in the stable group for LAD stenoses (41.5 +/- 15.1% vs 32.3 +/- 14.5%, p less than 0.03), while in RCA stenoses the results in the stable group were better (45.1 +/- 17.6% vs 32.7 +/- 12.3%, n.s.). One acute vessel occlusion necessitating an emergency bypass operation occurred in each group (2%). The patient in the stable group died (total mortality rate 1%). Sixty-three of the successfully treated patients were routinely restudied 6 months later. According to clinical symptoms, 23% of the stable and 36% of the unstable group were in functional classes III and IV. From the anatomical viewpoint, a restenosis (greater than 85%) was found in 17% of the stable and in 24% of the unstable group. A further spontaneous decrease (greater than 10%) of the vessel obstruction was found in 47% of the stable group and in 12% of the unstable group.(ABSTRACT TRUNCATED AT 250 WORDS)

Cognitive and motor development in preschool and school-aged children after neonatal arterial switch operation

OBJECTIVEnThe developmental status of children beyond 3 years of age after the neonatal arterial switch operation has not yet been systematically evaluated and is the topic of the present work.nnnMETHODSnSeventy-seven unselected children operated on as neonates with combined deep hypothermic circulatory arrest and low-flow cardiopulmonary bypass were examined at an age of 3.2 to 9.4 years (5.4 +/- 1.6 years, mean +/- standard deviation). Clinical neurologic status, standard scores of intelligence, acquired abilities and vocabulary, and standardized tests on gross motor and fine motor functions were carried out, and the results were related to preoperative, perioperative, and postoperative status and management.nnnRESULTSnNeurologic impairment was more frequent (9.1%) than in the normal population. Intelligence was not different in these patients compared with normal children (p = 0.11), but motor function, vocabulary, and acquired abilities were poorer. Reduced intelligence was found in 9.1%, fine motor dysfunction in 22.1%, and gross motor dysfunction in 23.4% of the children. Intelligence was weakly but significantly inversely related to the duration of bypass (Spearman correlation coefficient -0.25, p = 0.03) and tended to be inversely related to the duration of circulatory arrest (-0.21, p = 0.07), but not to core cooling time on bypass or degree of hypothermia. Gross motor function, vocabulary, and acquired abilities were not significantly related to any of the perioperative parameters considered. No correlation was found between the test results and the variables perinatal asphyxia, perioperative and postoperative cardiocirculatory insufficiency, resuscitation events, and plexal or intraventricular cerebral hemorrhage.nnnCONCLUSIONSnThe neonatal arterial switch operation with combined circulatory arrest and low-flow bypass in our experience is associated with neurologic as well as fine and gross motor impairment but appears to be well tolerated concerning cognitive functions as based on formal intelligence testing.

Recovery of regional left ventricular dysfunction after coronary revascularization. Impact of myocardial viability assessed by nuclear imaging and vessel patency at follow-up angiography

OBJECTIVESnThis study sought to evaluate an imaging approach using technetium-99m sestamibi scintigraphy and positron emission tomography with fluorine-18 fluorodeoxyglucose for assessment of myocardial viability proved by serial quantitative left ventricular angiography. Furthermore, the influence of successful long-term revascularization on functional recovery was studied.nnnBACKGROUNDnPrevious studies using positron emission tomography of myocardial perfusion and metabolism have demonstrated accurate identification of myocardial viability. However, most of these studies used a qualitative or semiquantitative wall motion analysis approach.nnnMETHODSnNuclear imaging with semiquantitative analysis of tracer uptake was performed in 193 patients with regional wall motion abnormalities. Regions were categorized as normal, viable with perfusion/metabolism mismatch, viable without mismatch (intermediate) and scar. Seventy-two of 103 patients with subsequent revascularization underwent follow-up angiography. In 52 of 72 patients, changes in regional wall motion were measured by the centerline method from serial angiography.nnnRESULTSnWall motion improved in mismatch regions from -2.2 +/- 1.0 to -1.1 +/- 1.4 SD (p < 0.001). In contrast, regions with an intermediate pattern and those with scar did not improve. Restenosis or graft occlusion influenced functional outcome because regions with preoperative mismatch and successful long-term revascularization improved at follow-up (from -2.3 +/- 1.0 to -0.8 +/- 1.4 SD, p < 0.001), whereas wall motion did not change with recurrent hypoperfusion. Metabolic imaging added diagnostic information, particularly in regions with mild and moderate perfusion defects.nnnCONCLUSIONSnThis imaging approach allows detection of viability in regions with myocardial dysfunction. Wall motion benefits most in myocardium with perfusion/metabolism mismatch and successful long-term revascularization.

Long term behavioural outcome after neonatal arterial switch operation for transposition of the great arteries

Aims: To evaluate behavioural outcome and quality of life in children aged 8–14 years after neonatal arterial switch operation for transposition of the great arteries. Methods: Sixty children operated as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass were evaluated at age 7.9–14.3 years by the Child Behaviour Checklist (CBCL) and the Inventory for the Assessment of the Quality of Life in Children and Adolescents (IQCL). Results: Parent reported behavioural outcome on all CBCL problem and competence scores was worse, whereas quality of life on self reported IQCL scores was not reduced compared to the normal population. On multivariate analysis, severe preoperative hypoxia was related to parent reported social problems; peri- and postoperative cardiocirculatory insufficiency was associated with internalising, externalising, attention, and total behavioural problems. Reduced expressive language was associated with total behavioural problems, and poor academic achievement was related to parent reported deficits in school performance. Impaired neurological status and reduced endurance capacity both predicted self reported stress by illness. Conclusions: The neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with parent reported long term behavioural impairment, but not with self reported general reduction in quality of life. This discrepancy may be a result of different perception of illness. In our experience, increased risk of long term psychosocial maladjustment after neonatal corrective cardiac surgery is related to the presence of neurological impairment and reduced endurance capacity.

Influence of temperature during cardiopulmonary bypass on leukocyte activation, cytokine balance, and post-operative organ damage

This study examined the hypothesis that core temperature (T(o)) during cardiopulmonary bypass (CPB) influences the perioperative systemic inflammatory response and post-operative organ damage. Twenty-four pigs were assigned to a T(o) regimen during CPB: normothermia (T(o) 37 degrees C; n = 8), moderate hypothermia (T(o) 28 degrees C; n = 8), or deep hypothermia (T(o) 20 degrees C; n = 8). Perioperative leukocyte activation, endotoxin release, and production of tumor necrosis factor-alpha (TNFalpha) and interleukin-10 (IL10) were examined with regard to post-operative organ damage, which was scored at histological examination of tissue probes of heart, lungs, liver, kidney, and ileum, taken 6 h after CPB. Total blood leukocyte count and TNFalpha plasma levels during CPB were significantly lower and IL10 levels were significantly higher in the moderate hypothermic group than in both other groups. Elastase activity, leukotriene B4-, and endotoxin levels were not affected by T(o) regimen. Moderate hypothermia was associated with the lowest histological organ damage score and normothermia with the highest. In all animals organ damage score for heart, lungs, and kidneys correlated significantly with TNFalpha levels at the end of CPB. Our data demonstrate a clear relationship between TNFalpha production during cardiac operations and post-operative multiple-organ damage. Moderate hypothermia, by stimulating IL10 synthesis and suppressing TNFalpha production during CPB, might provide organ protection.

Closure of atrial septal defects via limited right anterolateral thoracotomy as a minimal invasive approach in female patients

OBJECTIVEnThe closure of atrial septal defects via sternotomy is a low-risk and high-benefit procedure. Limited right anterolateral thoracotomy is an alternative approach with regard to cosmetic aspects. However, it is discussed that a lateral approach is not appropriate for more complex lesions and is associated with an increased incidence of phrenic nerve damage.nnnMETHODS AND RESULTSnThe perioperative and long-term outcomes (mean follow-up time: 73.2 months) of 87 female patients, mean age 20.4 years (range: 3-56 years), operated on for all types of atrial septal defects via limited right anterolateral thoracotomy between 1982 and 1993, were analysed retrospectively. Special features of the operation technique were a limited skin incision, protection of mammary gland tissue, prevention of phrenic nerve damage, and aortic cannulation in all patients. There were no intraoperative complications. Postoperative complications occurred in 12/87 patients including one rethoracotomy for postoperative bleeding and one late pericardial tamponade due to coumadine overdose. Follow-up was assessed by a survey obtained by the patients or their parents, and their family doctors in 79 patients (90.8%) Cardiac symptoms, mostly supraventricular arrhythmias, were observed in 13.9%. Echocardiography revealed mild tricuspid valve regurgitation (one patient) and mild mitral valve incompetence (one patient with ostium primum defect); there were no residual shunts. Cosmetic results were considered good and excellent in 87.3% and satisfactory in 8.9%. Three patients (3.8%) complained of a broad scar. Anaesthetic areas and optional scar pain were quite frequent (16.5%), whereas restriction of shoulder movement, breast asymmetry and scoliosis were rare. In summary, only one patient, suffering from intercostal neuralgia, would prefer sternotomy.nnnCONCLUSIONnLimited right anterolateral thoracotomy has a high cosmetic acceptance and was proven to be safe and effective for closure of any kind of atrial septal defects. Therefore, it is recommended as standard approach for atrial septal defects especially in female patients. reserved.

Influence of low-dose aprotinin on the inflammatory reaction due to cardiopulmonary bypass in children

BACKGROUNDnThe serine protease inhibitor aprotinin inhibits trypsin, kallikrein, and plasmin and enhances the complement hemolytic activity of the first complement component C1. We tested whether low-dose aprotinin influences the inflammatory reaction related to cardiopulmonary bypass.nnnMETHODSnIn an open, randomized study, 25 children undergoing cardiac operations were investigated prospectively. The treated group comprised 11 patients receiving low-dose aprotinin (20,000 kIU/kg [2.8 mg/kg]), and the control group included 14 patients. Complement activation, cytokine production, and leukocyte stimulation were analyzed before, during, and after cardiopulmonary bypass.nnnRESULTSnIn all children, significant C3 conversion and C5a generation, interleukin-6 synthesis, and myeloperoxidase, eosinophil cationic protein, and histamine liberation occurred in relation to cardiopulmonary bypass. This was not influenced by aprotinin treatment. In contrast, neutrophil kinetic studies at the end of cardiopulmonary bypass showed a significantly lower increase in the aprotinin as compared with the control group.nnnCONCLUSIONSnOur results suggest that low-dose aprotinin has little influence on the inflammatory reaction induced by cardiopulmonary bypass. Aprotinin affects neutrophil mobilization but not white blood cell degranulation related to cardiopulmonary bypass, and has no influence on complement activation and interleukin-6 synthesis.

Pulmonary embolectomy: review of a 15-year experience and role in the age of thrombolytic therapy.

OBJECTIVEnSurgical intervention for fulminant pulmonary embolism is nowadays most commonly restricted to patients with failure of or contraindication to thrombolytic therapy. Such a second choice indication may alter operative risks or late outcome, and this was investigated in a retrospective study.nnnMATERIAL AND METHODSnThirty-six patients (17 male, mean age: 50.6 +/- 15.5 years) with fulminant pulmonary embolism of either the pulmonary trunk or one of the pulmonary arteries and at least one contralateral segment underwent pulmonary embolectomy on cardiopulmonary bypass during a 15-year period (1979-89: 31 patients, group I; 1990-94: 5 patients, group II). Group II included only patients who did not meet the criteria for acute thrombolysis. All patients were in strongly compromised circulatory conditions (29/36 high dose catecholamines, 20/36 mechanical ventilation, 14/36 pre-operative cardiopulmonary resuscitation).nnnRESULTSnThe perioperative mortality rate was 26% in group I (8/31 patients, 7 with pre-operative cardiac arrest) and 20% in group II (1/5 patients not related to failure of previous thrombolytic therapy). Severe but non-fatal complications occurred in six patients who fully recovered following treatment. Follow-up was completed to 93% (25/27 patients) and comprised a total of 248 patient-years (mean: 119 months). Twenty-three out of 25 patients (92%) were in functional class I or II (NYHA). No recurrent pulmonary embolism or late clinical symptoms related to embolectomy were observed. One patient died 8 years postoperatively (late mortality: 0.4% patient-year). There was no difference between group I and group II regarding perioperative mortality, complications and late results.nnnCONCLUSIONSnLate results after pulmonary embolectomy are excellent in respect to functional class and late mortality. Early mortality is closely associated with preoperative cardiac arrest. Previous thrombolysis does not alter the perioperative risks, occurrence of complications or late outcome after surgical intervention.